Engineering topics

Lee, David

Publications and source records attributed to Lee, David.

At least 19 records

DOE OSTI2022

Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition

Presequence protease (PreP), a 117kDa mitochondrial M16C metalloprotease vital for mitochondrial proteostasis, degrades presequence peptides cleaved off from nuclear-encoded proteins and other aggregation-prone peptides, such as amyloid β (Aβ). PreP structures have only been determined in a closed conformation; thus, the mechanisms of substrate binding and selectivity remain elusive. Here, we leverage advanced vitrification techniques to overcome the preferential denaturation of one of two ~55 kDa homologous domains of PreP caused by air-water interface adsorption. Thereby, we elucidate cryoEM structures of three apo-PreP open states along with Aβ- and citrate synthase presequence-bound PreP at 3.3–4.6 Å resolution. Together with integrative biophysical and pharmacological approaches, these structures reveal the key stages of the PreP catalytic cycle and how the binding of substrates or PreP inhibitor drives a rigid body motion of the protein for substrate binding and catalysis. Together, our studies provide key mechanistic insights into M16C metalloproteases for future therapeutic innovations.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Impacts of Substrate Thinning on FPGA Performance and Reliability [Slides]

Substrate thinning is necessary in devices with flip-chip BGA packages to enable both radiation testing and component qualification and high-spatial resolution beam-based failure analysis methods. We investigated three factors affecting device performance: subsurface damage from the thinning process, reduced heat spreading in thin substrates, and changes in device switching speed. We conclude subsurface damage to crystalline Si caused by the thinning process is removable with sufficient SiO 2 slurry polishing. Local temperature differences increase minimally in devices thinned to 3 μm. Compressive stress in the Si increases globally after device thinning and leads to slowing of ring oscillator frequency by about 0.5% compared to full-thickness devices. Future work will include extending the results to submicron Si thickness values, which also has important benefits for failure analysis, debug, and security assessments. We also plan to extend this type of work to other FPGAs and other devices like memory and processors.

36 MATERIALS SCIENCE↗

DOE OSTI2021

The homogenous alternative to biomineralization: Zn- and Mn-rich materials enable sharp organismal “tools” that reduce force requirements

We measured hardness, modulus of elasticity, and, for the first time, loss tangent, energy of fracture, abrasion resistance, and impact resistance of zinc- and manganese-enriched materials from fangs, stings and other “tools” of an ant, spider, scorpion and nereid worm. The mechanical properties of the Zn- and Mn-materials tended to cluster together between plain and biomineralized “tool” materials, with the hardness reaching, and most abrasion resistance values exceeding, those of calcified salmon teeth and crab claws. Atom probe tomography indicated that Zn was distributed homogeneously on a nanometer scale and likely bound as individual atoms to more than ¼ of the protein residues in ant mandibular teeth. This homogeneity appears to enable sharper, more precisely sculpted “tools” than materials with biomineral inclusions do, and also eliminates interfaces with the inclusions that could be susceptible to fracture. Based on contact mechanics and simplified models, we hypothesize that, relative to plain materials, the higher elastic modulus, hardness and abrasion resistance minimize temporary or permanent tool blunting, resulting in a roughly 2/3 reduction in the force, energy, and muscle mass required to initiate puncture of stiff materials, and even greater force reductions when the cumulative effects of abrasion are considered. We suggest that the sharpness-related force reductions lead to significant energy savings, and can also enable organisms, especially smaller ones, to puncture, cut, and grasp objects that would not be accessible with plain or biomineralized “tools”.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Preliminary Results from Heavy-Ion Irradiation of the Xilinx Versal ACAP.

Abstract not provided.

Lee, David↗

DOE OSTI2021

InterSpec v. 1.0.9

SAND2021-4823 O InterSpec decodes and displays gamma radiation data from a variety of handheld, laboratory, and fixed installation detector types. Once loaded, InterSpec provides a means to interactively analyze the data via a peak-based methodology. InterSpec assists with isotope identification and determines the source strength and shielding characteristics of the measured item. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.

Johnson, William↗

DOE OSTI2021